Burgeoning tool of biomedical applications - Superparamagnetic nanoparticles

Highlights

• A review of biomedical applications of magnetic nanoparticles is discussed.

• Nanosize, superparamagnetism, biocompatibility, surface coatings are described.

• Includes relevant research on Iron oxide, ferrites of Ni, Co, Mn, Zn, Ca, K.

• Role and need of folic acid conjugation is discussed.

• Various challenges and associated problems are explained.

Abstract

This review offers a hierarchical preview of the emergence of magnetic nanoparticles (MNPs) and their composites in the biomedical field providing an insight into their essential features. The need for coating their surfaces with stabilizers such as polyethylene glycol (PEG) and silica has also been explained. This is required for reducing their agglomeration and appropriate functionalization for final application. A magnetic material for such an application is required to be nanosized, superparamagnetic and biocompatible; all these requisites have been well discussed. Various research conducted on magnetic materials as maghemite, magnetite and ferrite based nanoparticles of Ni, Co, Mn, Zn, Ca and K have been described in detail, along with their composites such as PEG and silica. Folic acid conjugation is done on the coated MNPs as folate receptors are over-expressed on the tumor cells; this makes their targeting efficiency better and precise. In addition, various challenges associated with magnaetic nanoparticles/nanocomposites such as nanoparticle-biomolecule interface, drug loading, drug release properties, blood barrier etc., which inhibit their desired role, have also been described.

Introduction

It all began with the famous talk of Dr. Richard Fenyman, at Caltech, in December 1959, that “There is plenty of room at the bottom”. This talk acted as a “seed of thought” that planted the tremendous and wide-spread potential of nanomaterials in the minds of researchers world-wide. One of the most benefitted areas that have witnessed a revolutionary change due to its amalgamation with nanotechnology is biomedicine. The evolution of medicinal science, diagnostics and therapeutic treatments has seen a tremendous upsurge from the medieval medicines to the latest contemporary techniques, which involve nanotechnology. In recent times, magnetic nanoparticles have been scrutinized as a potential tool for many biomedical applications. Magnetic Nanoparticles (MNPs) as the name suggests, represent the class of materials whose dimensions fall in the nano-scale and being inherently magnetic can be controlled with an external magnetic field [1]. This helps in tracking their movement inside the body and gives clinicians flexibility as well as control while carrying out any procedure. The magnetic properties are extremely sensitive to size, composition, and local atomic environment [2]. This review summarizes different magnetic nanomaterials that have been studied for various biomedical applications. Basically, there are two types of approaches by which MNPs bind to the desired targeted tissues – passive and active. Mechanism of passive targeting includes enhanced permeation and retention (EPR). It works on the principle that in the rush to grow speedily, tumor cells produce new vessels with poor organization and leaky surface which enables the penetration of NPs into the tumor tissue. Pertaining to ineffective lymphatic drainage, NPs accumulate selectively with reduced clearance. However, passive targeting is limited to certain tumors and is challenging to effectively manage as it is dependent on many factors such as capillary conditions, blood barrier, and rate of drainage. In active targeting, surface of NPs is modified with targeting ligands which work in a lock and key manner, i.e. receptors on the ligand bind to specific cells only thereby enhancing the targeting efficiency. Folic acid conjugation is an example of such targeting. Binding capability of MNPs is dependent on density and molecular orientation of the targeting ligand, size and shape of MNPs.

For targeted drug delivery applications, the basic idea is to encapsulate or attach any therapeutic drug to magnetic nanoparticles/nanocomposite. Using external magnetic field, this nanocomposite can be directed to the desired site, where by some triggering action such as pH change, the drug gets released. Apart from drug delivery applications, magnetic resonance imaging (MRI) is another area in which MNPs have been reported to be very promising. MR imaging is a non-invasive technique for obtaining anatomical, molecular, metabolic and physiological analysis with high spatial as well as temporal resolution. It is based on the principle that on applying magnetic field, nuclear magnetization of hydrogen atoms in the body gets aligned and, on its removal, nuclei relax back to its original state. The following parameters are measured from the obtained MR image - longitudinal (T₁) and transverse (T₂) relaxation, (T₂*) relaxation, r₁ (1/T₁) relaxivity, r₂ (1/T₂) relaxivity, r₂*(1/T₂*) relaxivity. Image contrast is formed on variation in the rate of relaxation that enables to distinguish between tissues and malignancies. In 1970s, Widder, Senyei and colleagues introduced magnetic micro and nanoparticles for biomedical applications [3]. Iron oxide based materials are safe and currently been used. Apart from these, superparamagnetic ferrites have also been studied which have been discussed in the later section.